EP2981539A1

EP2981539A1 - Method for preparing oxyborane compounds

Info

Publication number: EP2981539A1
Application number: EP14719108.4A
Authority: EP
Inventors: Thibault Cantat; Christophe GOMES; Enguerrand BLONDIAUX; Olivier JACQUET
Original assignee: Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Current assignee: Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Priority date: 2013-04-03
Filing date: 2014-04-01
Publication date: 2016-02-10
Anticipated expiration: 2034-04-01
Also published as: FR3004181A1; US20160052943A1; FR3004181B1; EP2981539B1; US9890180B2; WO2014162266A1

Abstract

The present invention concerns a method for preparing oxyborane compounds of formula (I): using carbon dioxide, and the use of the oxyborane compounds obtained in this way for preparing methane derivatives, in particular oxygenated, halogenated or amino derivatives of methane. The methane derivatives obtained in this way can then be used in the production of vitamins, pharmaceutical products, glues, acrylic fibres and synthetic leathers, pesticides, and fertilisers, for example. The invention also concerns a method for producing vitamins, pharmaceutical products, glues, acrylic fibres, synthetic leathers, pesticides, and fertilisers, for example, comprising a step of preparing methane derivatives, in particular oxygenated, halogenated or amino derivatives of methane, from oxyborane compounds obtained by the method according to the invention. The present invention further concerns a method of preparing labelled oxyborane compounds and the use of same.

Description

PROCESS FOR THE PREPARATION OF OXYBORAN COMPOUNDS

The present invention relates to a process for the preparation of oxyborane compounds using carbon dioxide and the use of the oxyborane compounds thus obtained, for the preparation of methane derivatives, in particular, oxygenated, halogenated or amine derivatives of methane. The methane derivatives thus obtained can then be used in the manufacture of vitamins, pharmaceuticals, glues, acrylic fibers and synthetic leathers, pesticides, and fertilizers, for example.

The invention also relates to a process for producing vitamins, pharmaceuticals, glues, acrylic fibers, synthetic leathers, pesticides, and fertilizers, for example, comprising a step of preparing the methane derivatives, in particular , oxygenated, halogenated or amine derivatives of methane, from oxyborane compounds obtained by the process according to the invention.

The present invention further relates to a process for the preparation of labeled oxyborane compounds and their uses.

The use of C0 ₂ as a carbon source for the production of chemical consumables is a major challenge to reduce its atmospheric accumulation but also to control our dependence on fossil fuels.

The biggest challenge facing scientists and industrialists is to recycle C0 ₂ , which is to develop reactions that produce chemical compounds such as fuels, plastic polymers, drugs, detergents, high tonnage molecules, traditionally obtained by petrochemical methods. The technical difficulty lies in the development of chemical reactions that make it possible to functionalize C0 ₂ while reducing the carbon center (ie by substituting the C-O bonds of C0 ₂ by CH or CC bonds).

Catalytic reduction of C0 ₂ to formic acid HCOOH, formaldehyde

H ₂ CO, methanol CH ₃ OH and methane CH _{4 are} attracting increasing interest in the search for new synthetic fuels. In this context, the major reduction processes can be classified according to the nature of the reducer used, as indicated in paragraphs 1 to 4, below. The use of strong reducing agents, such as alkali metals (Li, Na, K) or metal hydrides (aluminum hydride, borohydrides, etc.), is discarded because these reactants lead to strongly exothermic reactions in the presence of CO ₂ and therefore do not allow to ensure a favorable energy balance during the reduction of carbon dioxide. 1. Electro-and photoelectrochemical methods

The use of electrons provided by an electrolytic assembly to reduce C0 ₂ remains a very dynamic field of research and motivated by the hope of finding efficient and selective catalysts, allowing, for example, to selectively reduce C0 ₂ in the presence protons, while avoiding the formation of dihydrogen ¾ (EE Benson, CP Kubiak, AJ Sathrum, JM Smieja, Chem Soc Rev. 2009, 38, 89). Photoelectro-reduction processes are also under study (Y. Izumi, Coord Chem Rev 2013, 257, 171).

2. Hydrogenation of CO2

The reaction between CO ₂ and dihydrogen can lead to the formation of formic acid (in the presence of a base), methanol or methane. Molecular (so-called homogeneous) catalysts and heterogeneous catalysts have been described to facilitate this reaction (PG Jessop, T. Ikariya, R. Noyori, Chem Rev. 1995, 95, 259, W. Wang, S. Wang, J. Gong, 2011, 3703). 3. Hydrosilylation of CO2

The reaction between C0 ₂ and hydrosilanes (characterized by the presence of an Si-H bond) makes it possible to reduce the C0 ₂ to formoxysilane, bis (silyl) acetals and methoxysilanes which can, after hydrolysis, be carried out with formic acid HCOOH, to formaldehyde H ₂ CO and methanol CH ₃ OH, respectively (SN Riduan, YG Zhang, JY Ying, Angew Chem Int, Ed., 2009, 48, 3322, A. Berkefeld, WE Piers, M. Parvez, J. Am., Chem Soc., 2010, 132, 10660). Certain catalysts also make it possible to reduce CO ₂ directly to methane (Matsuo, T., A. Ka aguchi, J. Am., Chem., Soc., 2006, 128). In these reactions, siloxanes and silanols are formed as by-products. 4. Hydroboration of C0 ₂

The reaction between C0 ₂ and a hydroborane of formula (I) is called the C _{2 2} hydroboration reaction. This transformation requires the use of a catalyst. Three different catalytic systems are known to date. They are detailed below.

• The Hairong Guan group (University of Cincinnatti, USA) developed the first C0 ₂ hydroboration catalyst in 2010 (S. Chakraborty, J. Zhang,

JA Krause, HR Guan, J. Am. Chem. Soc. 2010, 132, 8872; S. Chakraborty, YJ Patel, JA Krause, HR Guan, Polyhedron 2012, 32, 30; S. Chakraborty, J. Zhang, YJ Patel, JA Krause, HR Guan, Inorg. Chem. 2013, 52, 37). It is a nickel complex which makes it possible to carry out the reduction of C0 ₂ in methoxyborane. Formoxyborane is observed as a reaction intermediate. The hydroboranes used are catecholborane (catBH), 9-borabicyclo [3.3.1] nonane (9-BBN) and pinacholborane (pinBH). The catalyst operates at room temperature and in the presence of 1 bar of CO ₂ . With the catecholborane, the number of rotation of the catalyst (in English Turn-Over Number or TON, defined below) is 495 to 25 ° C and its frequency of rotation (in English Tu n-Over Frequency or TOF, defined ci below) of 495 hr ^-1 This reaction is shown in Figure 1 below.

2 catalyst _. ZZ

\ (0.2 to 1 mol%) \ \ /

C0 ₂ + B- H * · B-OCH ₃ + B-O- B

/ benzene / / \

1 bar ^z 25 "C ^z ZZ IV) (V)

catecholborane pinacholborane 9-

(catBH) (pinBH) borabicyclo [3.3.1] nane (9-BBN)

Diagram 1

In the above diagram as well as in the remainder of the description, the TON and the TOF are defined as follows: amount of borane (R ¹ R ² BH) at the end of the reaction 100

ON =

amount of borane ( ¹ R ^J 8H) at the beginning of the reaction catalytic charge in mol of borane at the end of the reaction 100

OF =

amount of borane at the beginning of the reaction catalytic charge in mol% reaction time in hours Thus, the higher the TON and the TOF, the more effective the catalyst is.

• In 2012, Sylviane Sabo-Etienne's group (CNRS, Toulouse, France) described a catalyst based on a ruthenium hydride complex for the C _{2 2} hydroboration reaction (S. Bontemps, L, Vendier, S. Sabo -Etienne, Angew Chem Int.Ed 2012, 51, 1671). The authors have shown that the CO ₂ hydroboration reaction can lead to bis (boryl) acetals and boroxymethylformate (R'R 1 -OCH 2 OCHO) intermediates. These intermediates have not been isolated.

Only pinacholborane was used and a large load of catalyst was used (10 mol%). Under these conditions, the activity of the catalyst is low and the formation of methoxyborane requires 22 days of reaction at room temperature or 5 hours at 70 ° C. This reaction is shown in Scheme 2 below.

pinacholborane (pinBH)

Figure 2

In 2012, Douglas W. Stephan's group (University of Toronto, Canada) described a ruthenium catalyst for C0 ₂ hydroboration (MJ Sgro, DW Stephan, Angew Chem Int, Ed 2012, 51). , 11343). Catecholborane and 9-borabicyclo [3.3.1] nonane were used as reagents. They do not show a difference in reactivity. The reaction is slow at 50 ° C with a catalyst load of 1.0 mol%. This reaction is shown in Scheme 3 below. zzz catalyst

(0.2 to 1 mol%) \ \ / co ₇ + B-OCH ₃ + B-O- B

/ benzene / / \

1 bar 25 ° C

oiborane

catechoiborane (catBH) 9-borabicyclo [3.3.1] nonane (9-BBN) Scheme 3

Transformations involving reaction promoters (such as mixtures Mes ₃ P / AlCi ₃ or Mes ₃ P / AlBr ₃ (Mes = mesityl)) in stoichiometric, that is to say non-catalytic quantities, also been described by

G. Menard, D. W. Stephan, J. Am. Chem. Soc., 2010, 132, 1796.

The conversion of C0 ₂ into chemical consumables such as, for example, methane derivatives, in particular, oxygenated, halogenated or amine derivatives of methane, especially formic acid, formaldehyde and methanol, methane, methyl halide and Methylamine, by a hydroboration reaction of C0 _{2 is} of growing interest. The reaction of C0 ₂ with a hydroborane taking place in two steps leads to interesting synthetic intermediates of formoxy borane type (R ¹ R ² B-O-CHO), methoxyborane (R ¹ R ² B-O-CH ₃ ) or bis (boryl) acetals (R ¹ R ² B-O) ₂ CH ₂ ). These intermediates, which may also be more generally referred to as "oxyborane compounds" because of the presence of "RR BO-" in these compounds, are stable and readily lend themselves to different types of reaction to lead to various chemical compounds such as formic acid, formaldehyde, methanol, methane, methyl halide, methylamine, etc.

However, given the high thermodynamic stability of carbon dioxide, its conversion to oxyborane compounds must necessarily use efficient catalysts so as to promote the thermodynamic balance of this chemical transformation. Furthermore, the hydroboration reaction requires the use of an effective catalyst because in its absence, the product resulting from this chemical transformation can not be obtained measurably in a short time (less than a week) and at a minimum. temperature below 150 ° C.

However, to date, the hydroboration reactions of C0 ₂ involve a limited number of catalysts which, in addition, are essentially often expensive and / or toxic transition metal complexes such as nickel or ruthenium.

In the context of the conversion of C0 ₂ ar a hydroboration reaction, firstly in "oxyborane compounds" and then in chemical consumables such as, for example, methane derivatives, in particular, oxygenated, halogenated or amine derivatives of methane Formic acid, formaldehyde, methanol, methane, methyl halide and methylamine, the technical challenge is to develop effective catalysts that overcome the problems of toxicity and costs generally. associated with the use of known metal catalysts, especially catalysts based on precious metals.

There is therefore a real need for a catalyst allowing the conversion of C0 ₂ and a hydroborane to oxyborane compounds, by a hydroboration reaction, which is effective (capable of increasing the rate of conversion of C0 ₂ even in small quantities), selective (favoring the production of the desired product compared to the by-products), inexpensive and / or not very toxic compared with known catalysts for converting C0 ₂ to oxyborane compounds by this type of reaction.

In particular, there is a real need for a catalyst, as defined above, which does not contain:

- Group II A alkaline earth metals from the Periodic Table of Elements (such as magnesium and calcium);

transition metals from Group IB to VIIIB of the Periodic Table of the Elements (such as nickel, iron, cobalt, zinc, copper, rhodium, ruthenium, platinum, palladium, iridium);

rare earths whose atomic number is between 57 and 71 (such as lanthanum, cerium, praseodymium, neodymium); or

- actinides whose atomic number is between 89 and 103 (such as thorium, uranium). On the other hand, oxyborane compounds, incorporating radioisotopes and / or isotopes that are stable and capable of being converted into various labeled chemical compounds such as formic acid, formaldehyde, methanol, methane, methyl halide, methylamine, etc. . are of particular interest in many fields such as, for example, life sciences (study / elucidation of enzymatic mechanisms, biosynthetic mechanisms, biochemistry, etc.), environmental sciences (tracing of waste, etc.). ), research (study / elucidation of reaction mechanisms) or research and development of new pharmaceutical and therapeutic products. Thus, developing a process for the preparation of labeled oxyborane compounds meeting the above requirements can meet a real need.

There is, therefore, a real need for a process which makes it possible to prepare labeled oxyborane compounds incorporating stable radioisotopes and / or isotopes, from labeled reagents such as, for example, CO ₂ and / or a labeled hydroborane (s). ).

The present invention is specifically intended to meet these needs by providing a process for preparing oxyborane compounds of formula (I):

in which

R ¹ and R ² independently of one another are hydrogen, halogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, a silyl group, a siloxy group, an amino group, an alkoxy group, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy, amino and alkoxy groups being optionally substituted, or

R ¹ and R ² , taken together with the boron atom to which they are bonded, form an optionally substituted heterocycle,

^"Y represents -CHO, CH ₂ -0 ~ ^s BR-R ² with R ¹ and R ² as defined above, -CH _3,

R ¹ , R ² and Y optionally comprise, independently of one another, H, C, N, O, F, Si and / or S as defined below,

- H represents a hydrogen atom (H), deuterium (H) or tritium (H), - C represents a carbon atom ( ^I2 C), an isotope ⁿ C ^{,! 3} C or ¹⁴ C, N represents a nitrogen atom ( ¹⁴ N), a ¹⁵ N isotope,

O represents an oxygen atom ( ¹⁶ 0), an isotope ^I8 0,

F represents a fluorine atom ( ^I9 F), an ¹⁸ F isotope,

Si represents a silicon atom (Si), an Si or Si isotope,

S represents a sulfur atom ( ³² S), a ³³ S, ³⁴ S or ³⁶ S isotope, characterized in that a hydroborane of formula (II) is reacted in which R ¹ , R ² and H are such as defined above with C0 ₂ in which C and O are as defined above, and

in the presence of a catalyst selected from the group consisting of

i. organic bases selected from nitrogenous organic bases, phosphorus organic bases, carbon bases, or oxygenated organic bases;

ii. organic or inorganic boron compounds; or

iii. organic or inorganic compounds of aluminum.

Thus, the method of the invention makes it possible to prepare both oxyborane compounds of formula (I) unlabeled oxyborane compounds of formula (I) labeled.

The process of the invention also has the advantage of making it possible to convert CO ₂ into oxyborane compounds with a large choice of catalysts. The catalysts used in the process of the invention overcome the problems of toxicity and costs generally associated with the use of metal catalysts whose metal is

an alkaline earth metal of Group IIA of the Periodic Table of Elements (such as magnesium and calcium);

a Group IB to VIIIB transition metal of the Periodic Table of the Elements (such as nickel, iron, cobalt, zinc, copper, rhodium, ruthenium, platinum, palladium, iridium);

a rare earth whose atomic number is between 57 and 71 (such as lanthanum, cerium, praseodymium, neodymium); or an actinide whose atomic number is between 89 and 103 (such as thorium, uranium).

According to the conditions of the process of the invention, the oxyborane compounds can be obtained in the form of a mixture of compounds of formulas (I) or with a good selectivity (up to 100% in a single type of oxyborane compound of formula ( I)) ·

The process of the invention can lead to oxyborane compounds of formula (I) with a good or even excellent yield (ranging from 50% to 100%, for example).

In the context of the present invention, the yield is calculated relative to the amount of hydroborane of formula (II) introduced initially, on the basis of the amount of oxyborane compound of formula (I) isolated:

Yield (oxyborane) / (n (oxyborane) + n (hydroborane)) n being the amount of material

In the context of the present invention, the selectivity relates to the nature of the oxyborane products of formula (I) formed from the hydroborane of formula (II).

In order for the process of the invention to lead to the production of an oxyborane compound of formula (I), a judicious and adequate combination of hydroboranes of formula (II) and catalysts is essential. In particular, it is necessary for the hydroborane of formula (II) and the catalyst to be chosen, taking into account in particular their respective steric bulk, the reducing character of the hydroborane, the nucleophilic nature of the catalyst, and their solubility in the reaction medium. .

For the purposes of the present invention, the term "alkyl" means a linear, branched or cyclic, saturated or unsaturated, optionally substituted carbon radical comprising 1 to 12 carbon atoms. As linear or branched saturated alkyl, there may be mentioned, for example, the methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, nonyl, decyl, undecyl and dodecanyl radicals and their branched isomers. As cyclic alkyl, there may be mentioned cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicylco [2,1,1] hexyl, bicyclo [2,2,1] heptyl. Unsaturated cyclic alkyls include, for example, cyclopentenyl and cyclohexenyl. Unsaturated alkyls also referred to as "alkenyl" or "alkynyl" respectively contain at least one double or one triple bond. As such, there may be mentioned, for example, the radicals ethylenyl, propylenyl, butenyl, pentenyl, hexenyl, acetylenyl, propynyl, butynyl, pentynyl, hexynyl and their branched isomers. The alkyl group, within the meaning of the invention including the alkenyl and alkynyl groups, may be optionally substituted by one or more hydroxyl groups; one or more alkoxy groups; one or more halogen atoms selected from fluorine, chlorine, bromine and iodine atoms; one or more nitro groups (-NO ₂ ); one or more nitrile groups (-CN); one or more aryl groups, with the alkoxy and aryl groups as defined in the context of the present invention.

The term "aryl" generally refers to a cyclic aromatic substituent having from 6 to 20 carbon atoms. In the context of the invention, the aryl group may be mono- or polycyclic. As an indication, mention may be made of phenyl, benzyl and naphthyl groups. The aryl group may be optionally substituted by one or more hydroxyl groups, one or more alkoxy groups, one or more halogen atoms selected from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (-NO), one or more nitrile groups (-CN), one or more alkyl groups, with the alkoxy and alkyl groups as defined within the scope of the present invention.

The term "heteroaryl" generally denotes a mono- or polycyclic aromatic substituent comprising from 5 to 10 members, of which at least 2 are carbon atoms, and at least one heteroatom chosen from nitrogen, oxygen, boron and silicon. , phosphorus or sulfur. The heteroaryl group may be mono- or polycyclic. As an indication, mention may be made of furyl, benzofuranyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, thiophenyl, benzothiophenyl, pyridyl, quinolinyl, isoquinolyl, imidazolyl, benzimidazolyl, pyrazolyl, oxazolyl, isoxazolyl, benzoxazolyl, thiazolyl, benzothiazolyl, isothiazolyl, pyridazinyl groups. , pyrimidilyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl, quinazolinyl. The heteroaryl group may be optionally substituted by one or more hydroxyl groups, one or more alkoxy groups, one or more halogen atoms selected from fluorine, chlorine, bromine and iodine atoms, one or more nitro groups (-N (¾ ), one or more nitrile groups (-CN), one or more aryl groups, one or more alkyl groups, with the alkyl, alkoxy and aryl groups as defined within the scope of the present invention.

The term "alkoxy" means an alkyl group, as defined above, bonded through an oxygen atom (-O-alkyl).

The term "heterocycle" generally refers to a mono- or polycyclic substituent, having from 5 to 10 members, saturated or initiated, containing from 1 to 4 heteroatoms chosen independently of each other, among nitrogen, oxygen, boron, silicon, phosphorus or sulfur. As an indication, mention may be made of borolane, borole, borinane, 9-borabicyclo [3.3.1] nonane (9-BBN), 1,3,2-benzodioxaborole (catecholborane or catBH), pinacholborane (pinBH) morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, thianyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isotibiazolidinyl substituents. The heterocycle may be optionally substituted by one or more hydroxyl groups, one or more alkoxy groups, one or more aryl groups, one or more halogen atoms selected from fluorine, chlorine, bromine and iodine atoms, one or more groups. nitro (-N <¾), one or more nitrile groups (-CN), one or more alkyl groups, with the alkyl, alkoxy and aryl groups as defined within the scope of the present invention.

By halogen atom is meant an atom chosen from fluorine, chlorine, bromine or iodine atoms.

By "silyl group" is meant a group of formula [-Si (X) ₃ ] in which X is chosen from a hydrogen atom, one or more halogen atoms chosen from fluorine, chlorine, bromine or iodine, one or more alkyl groups, one or more alkoxy groups, one or more siloxy groups, one or more aryl groups, with alkyl, alkoxy and aryl groups as defined within the scope of the present invention.

By "siloxy" group is meant a silyl group, as defined above, linked by an oxygen atom (-O-Si (X) ₃ ).

By "amino" group is meant a group of formula -NR ^{3 4} , in which: R ³ and R ⁴ represent, independently of one another, a hydrogen atom, an alkyl group or an alkenyl group , an alkynyl group, an aryl group, a heteroaryl group, a heterocycle, a silyl group, a siloxy group, with alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy, as defined in the context of the present invention, or

^■ R ³ and R ^4, taken together with the nitrogen atom to which they are bonded, form a heterocycle optionally substituted by one or more hydroxyl groups; one or more alkyl groups; one or more alkoxy groups; one or more halogen atoms selected from fluorine, chlorine, bromine and iodine atoms; one or more nitro groups (-NO ₂ ); one or more nitrile groups (-CN); one or more groups aryl; with the alkyl, alkoxy and aryl groups as defined in the context of the present invention.

The substituents, and the radicals defined above groups may include, optionally, deuterium ^(2H), tritium ⁽³ H), ⁿ C, ¹³ C, ⁱ⁴ C, ¹⁵ N, ^{the! 8} 0, ¹⁸ F, ²⁹ Si, ³⁰ Si, ³³ S, ³⁴ S or ³⁶ S.

According to a preferred variant of the invention, in the oxyborane compound of formula (I) and in the hydroborane of formula (II),

^■ and R independently of one another, a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, said alkyl, aryl and alkoxy being optionally substituted, or

- R ¹ and R ² taken together with the boron atom to which they are bonded form an optionally substituted heterocycle.

Preferably, in the oxyborane compound of formula (I) and in the hydroborane of formula (II),

BR ^[ and R ² , represent, independently of one another, a hydrogen atom; an alkyl group selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or their branched isomers, cyclohexyl; an aryl group selected from benzyl or phenyl; or

^■ R ¹ and R ^2, taken together with the boron atom to which they are attached form a heterocycle, said heterocycle being selected from the catBH the pinBH or 9-BBN.

By catalyst, within the meaning of the invention is meant any compound capable of modifying, in particular by increasing, the speed of the chemical reaction in which it participates, and which is regenerated at the end of the reaction. This definition encompasses both catalysts, that is, compounds that exert their catalytic activity without the need for any modification or conversion, and compounds (also called pre-catalysts) that are introduced into the medium. and converted therein to a catalyst.

As already indicated, in the process of the invention, the catalyst may be (i) an organic base selected from nitrogenous organic bases, phosphorus organic bases, carbon bases, or oxygenated organic bases, with

the nitrogenous organic bases which may be secondary or tertiary amines chosen from, for example, triazabicyclodecene (TBD), N-methyltriazabicyclodecene (MeTBD), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), trimethylamine, teteamylamine, piperidine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo [2.2.2] octane (DABCO), proline, phenylalanine, a thiazolium salt, N diisopropylethylamine (DIPEA or DIEA) arginine; phospaines selected from, for example, tert-butylimino-tris (dimethylamino) phosphorane (P-t-Bu), tert-butylimino-tri (pyrrolidino) phosphorane (BTPP), tetramethyl (tris (dimethylamino) phosphoranylidene); phosphorictriamid-Et-imine (P2-Et), tert-octylimino-tris (dimethylamino) phosphorane (P 1 -t-Oct) and 1-tert-butyl-4,4,4-tris (dimethylamino) -2,2 bis [tris (dimethylamino) -phosphoranylidenamino] -2,5,4-catenadi (phosphazene) (P4-Bu);

the phosphorus-containing organic bases which may be alkyl or aryl phosphines chosen from, for example, triphenylphosphine, 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (B1 AP), triisopropylphosphine, 1,2-bis ( diphenylphosphino) ethane (dppe), tricyclohexylphosphine (PCy ₃ ); alkyl and aryl phosphonates selected from, for example, diphenylphosphate, triphenylphosphate (TPP), tri (isopropylphenyl) phosphate (TIPP), cresyldiphenyl phosphate (CDP), tricresylphosphate (TCP); alkyl and aryl phosphates selected from, for example, di-n-butyl phosphate (DBP), tris- (2-ethylhexyl) phosphate, triethyl phosphate; alkyl and aryl phosphinites and phosphonites selected from, for example, methyldiphenylphosphinite and methyldiphenylphosphonite; the aza-phosphines chosen from, for example, 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane (BV ^Me ) and 2,8,9- triisobutyl-2 ₅ 5,8,9-tetraaza-l-phosphabicyclo [3.3.3] undecane (BV ^iBu); the carbon bases for which the protonation takes place on a carbon atom, such as, for example, the N-hetero cyclic carbenes derived from an imidazolium salt chosen from 1,3-bis (2,6-diisopropylphenyl) salts; 1H-imidazol-3-ium, 1,3-bis (2,6-diisopropylphenyl) -4,5-dihydro-1H-imidazol-3-ium, 1,3-bis (2,4,6-trimethylphenyl) 1H-imidazol-3-ium, 1,3-bis (2,4,6-trimethylphenyl) -4,5-dihydro-1H-imidazol-3-ium, 4,5-dichloro-1,3-bis ( 2,6-diisopropylphenyl) -1H-imidazol-3-ium, 1,3-di-tert-butyl-1H-imidazol-3-ium (also called "ItBu" or "ItBu carbene" in the rest of the discussion ), 1,3-di-tert-butyl-4,5-dihydro-1H-imidazol-3-ium, said salts being in the form of chloride salts, for example; or oxygenated bases selected from, for example, hydrogen peroxide, benzoyl peroxide, pyridine oxide (PyO), N-methylmorpholine oxide or 1-oxidanyl-4-tetramoylpiperidine.

Examples of N-hetero ring carbenes are shown below;

In the process of the invention, the catalyst may also be (ii) an organic or inorganic boron compound chosen from, for example, BF ₃ , BF ₃ (Et ₂ 0), BCI 3, triphenyl hydroborane, tricyclohexyl hydroborane, B (C ₆ F ₅ ) ₃ , B-methoxy-9-borabicyclo [3.3.1] nonane, B-benzyl-9-borabicyclo [3.3.1] nonane (B-methoxy-9BBN), Me TBD-BBN ⁺ Γ, Me-TBD-BBN ⁺ CF ₃ S0 ₃ (TDB-BBN) ₂ , TBD-BBN-C0 ₂ or TBD-BBN-BBN.

As shown in Figure 4 below, (TDB-BBN) ₂ results from the dimerization of TBD-BBN, TBD-BBN-CO ₂ and TBD-BBN-BBN correspond to adducts between TBD-BBN and C0 ₂ or 9-BBN.

Figure 4

Me-TBD-BB Γ, (TDB ~ BBN) ₂ , TBD-BBN-CO ₂ and TBD-BBN-BBN can be obtained, for example, according to the protocols described in the experimental part. Me-TBD-BBN ⁺ CF ₃ S0 ₃ ^"as well as Me-TBD ~ BBN ⁺ X ^" in which X ^" is chosen from fluorine, chlorine and bromine can also be prepared by a protocol similar to that described for Me- TBD-BBN ⁺ F.

In the process of the invention, the catalyst may be, in addition, (iii) an organic or inorganic aluminum compound selected from, for example, AlCl ₃ , AlBr ₃ , aluminum isopropoxide or ethanoate. aluminum.

According to a preferred variant of the invention, the catalyst is (i) an organic base chosen from

nitrogenous bases, in particular triazabicyclodecene (TBD), N-methyltriazabicyclodecene (MeTBD), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), arginine; phosphazenes chosen from tert-butyliminotri (dimefhylamino) phosphorane (P1-t-Bu), tert-butylimino-tri (pyrrolidino) phosphorane (BTPP) and tetramethyl (tris (dimethylamino) phosphoranylidene) phosphorictriamid-Et-imine (P2-Et), tert-octylimino-tris (dimethylamino) phosphorane (P-t-Oct) and 1-tert-butyl-4,4,4-tris (dimethylamino) -2,2-bis [tris ( dimethylamino) -phosphoranylidenamino] -215.4-catenadi (phosphazene) (P4-Bu); phosphorus bases, especially 1, 2-bis (diphenylphosphino) ethane (dppe), tricyclohexylphosphine (PCy), 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo [3.3] .3] undecane (BV ^Me ), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane (BV ^iBu );

pyridine oxide (PyO); or

1,3-di-tert-butyl-1H-imidazol-3-ium or carbene ItBu.

The catalysts may, where appropriate, be immobilized on heterogeneous supports, for example, in order to ensure easy separation of said catalyst and / or its recycling. Said heterogeneous supports may be chosen from supports based on silica gel or on plastic polymers such as, for example, polystyrene; carbon supports selected from carbon nanotubes; silica carbide; alumina; or magnesium chloride (MgCl ₂ ).

In the process according to the invention, the reaction can be carried out under a CO ₂ pressure, by bubbling CO ₂ into the reaction medium or under a dry atmosphere containing CO ₂ (dried ambient air comprising, for example, about 78% by weight). volume of nitrogen, 21% by volume of oxygen, and from about 0.2 to 0.04% by volume of carbon dioxide). The reaction can also occur using supercritical CO ₂ .

Preferably, the reaction occurs under a CO ₂ pressure.

The pressure of C (¾, may then be between 0.2 and 75 bar, preferably between 0.2 and 30 bar, more preferably between 1 and 10 bar, inclusive.

The temperature of the reaction may be between 20 and 150 ° C, preferably between 20 and 125 ° C, more preferably between 20 and 70 ° C inclusive.

The duration of the reaction depends on the degree of conversion of the hydroborane of formula (II) and the nature of the oxyborane compound of formula (I) desired. The reaction may be carried out for a period of from 5 minutes to 300 hours, advantageously from 2 minutes to 250 hours, preferably from 10 minutes to 200 hours, inclusive.

The process of the invention, in particular the reaction between the different reactants, may take place in a mixture of at least two solvents chosen from:

ethers, preferably diethyl ether, or THF;

hydrocarbons, preferably benzene or toluene;

the nitrogenous solvents, preferably pyridine, or acetonitrile;

sulfoxides, preferably dimethyl sulphoxide; alkyl halides, preferably chloroform, or methylene chloride.

The various reagents used in the process of the invention (the hydroboranes of formula (II), the (pre-) catalysts, etc.) are, in general, commercial compounds or can be prepared by any process known to those skilled in the art. job.

The concentration of the hydroborane of formula (II) is from 0.1 to 2 mol / l, preferably from 0.3 to 1.5 mol / l, more preferably from 0.5 to 1.5 mol / l. This concentration is calculated on the basis of the volume of solvent introduced.

The amount of catalyst is from 0.00001 to 1 molar equivalent, preferably from 0.0001 to 0.1 molar equivalents, more preferably from 0.001 to 0.1 molar equivalents, inclusive, with respect to the hydroborane of formula ( II).

As indicated above, the oxyborane compounds of formula (I), prepared by the process of the invention, have the advantage of being easily amenable to different types of reaction to lead to various chemical compounds such as methane derivatives, in particular , oxygenated, halogenated or amine derivatives of methane, in particular formic acid, formaldehyde, methanol, methane, methylhalide, methylamine. For example, the hydrolysis of compounds of formula (I) under conditions known to those skilled in the art leads to formic acid when Y is -CHO, to formaldehyde when Y is -CLb-O-BPjR ² with R ¹ and R ² as defined above, and methanol when Y is -C¾. The oxyboranes of formula (I) may also react with a selected halohydric acid HF, HCl, HBr and HI. For example, the reaction of the oxyboranes of formula (I) with HI under conditions known to those skilled in the art leads to with methyl iodide when Y represents -CH. Methyl iodide can, in turn, be reacted with an amine to yield the corresponding methylamine as indicated in the REAXYS databases.

The subject of the invention is therefore the use of the oxyborane compounds of formula (I) obtained according to the process of the invention, for the preparation of methane derivatives, in particular, oxygenated, halogenated or aminated derivatives of methane, in particular formic acid, formaldehyde, methanol, methane, methyl halide derivatives and methylamines. The methane derivatives thus obtained can then be used in the manufacture of vitamins, pharmaceuticals, glues, acrylic fibers and synthetic leathers, pesticides, and fertilizers. This is another object of the invention.

The invention also relates to a process for producing vitamins, pharmaceuticals, glues, acrylic fibers, synthetic leathers, pesticides, and fertilizers, comprising a step of preparing the methane derivatives, in particular derivatives thereof. oxygenated, halogenated or amine methane, from oxyborane compounds obtained by the process according to the invention.

As already indicated, the process according to the invention leads to the formation of oxyborane compounds with a good or even excellent yield (ranging from 50% to 100%, for example), and good selectivity (up to 100% in a single type of oxyborane compound). In the case where the catalyst is supported, a simple filtration can make it possible to recover it and to eliminate any boron-based byproducts formed.

The process of the invention also makes it possible to prepare labeled oxyborane compounds of formula (I). This is another object of the invention. The labeled oxyborane compounds correspond to the oxyborane compounds of formula (I) comprising at least one radiolabel / radiotracer or a selected isotope.

Isotopes mean, for the same element, two atoms having the same number of protons (and electrons) but a different number of neutrons. Having the same number of electrons and protons, the chemical properties of the isotopes of the same element are almost identical. There may, however, be slight variations in the rate of a chemical reaction when one of the atoms of a reagent is replaced by one of its isotopes. On the other hand, as the nucleus does not have the same number of neutrons, the mass of the atoms varies which can make the atom unstable: that is why they can be radioactive. These are radioisotopes. In the context of the invention, the term "isotopes" may also include "radioisotopes".

Radiolabeling is the act of associating with a given molecule or compound an isotope that will make it possible to follow the evolution or / and the fixation of the molecules, for example, in an organ. The radiotracer is the radioactive element (s) present within a molecule to follow the path of this substance, for example, in an organ.

This process can thus allow access to the labeled oxyborane compounds of formula (I) and to their reaction product. For example, the reaction between a methoxyborane The corresponding labeled iodomethane is used in the synthesis of labeled methylamines (SC Choudhry, L. Serico, J. Cupano, Journal of Organic Chemistry, 1989, Vol 54, pp. 3755-3757). .

The use of molecules for tracing, metabolization, imaging, etc., is detailed in the literature (U. Pleiss, R. Voges, Synthesis and Applications of Isotopically Labeled Compounds, Volume 7, Wiley-VCH, 2001, R. Voges, JR Heys, T. Moenius, Preparation of Compounds Labeled with Tritium and Carbon-14, Wiley-VCH: Chippenham (UK) 2009).

The possibility of forming the labeled oxyborane compounds of formula (I) can be ensured by the availability of labeled reagents corresponding, for example, by:

- hydroboranes R ^! R ² BH marked ^2H (D), or ^3H (T) are obtained by deuteration dihydroboranes (RRB) ₂ in the presence of molecular deuterium D ₂ (CS Wei, CA Jimenez-Hoyos, MF Videa, JF Hartwig, MB Hall J. Am Chem Soc 2010, 132, 3078);

the hydroboranes R R BH labeled H (D) or H (T) are obtained by exchange

H / D in the presence of D ₂ molecular deuterium and R ^L R ² BH hydroborane (JY Wu, Moreau B, Ritter T, J. Am Chem Soc 2009, 131, 12915, JM Farrell, JA Hatnean, DW Stephan, J. Am Chem Soc 2012, 134, 15728, S. Bontemps, L. Vendier, S. Sabo-Etienne, Angew Chem Int.Ed 2012, 51, 1671);

the ² H (D) or ³ H (T) labeled R 2 BH hydroboranes are obtained using

BH ₃ (THF) as a borate reagent in the synthesis of hydroborane, instead of BH ₃ (THF) (Brown JM, GC Lloydjones, J. Am Chem Soc 1994, 116, 866);

- hydroboranes R ^! R ² BH labeled ² H (D) or ³ H (T) are obtained by reacting a boron halide of formula R ^! R ² BX (X = F, Cl, Br or I) with a labeled metal hydride, such as lithium hydride (LiH) or lithium tetrahydroaluminate (L1AIH ₄ ) (Y. Segawa, Y. Suzuki, M. Yamashita, Nozaki, J, Am., Chem., Soc., 2008, 130, 16069; ZP Lu, ZH Cheng, Chen ZX, LH Weng, ZH Li, Wang HD, Angew Chem Int, Ed., 2011, 50, 12227. ), the hydrides being available both in deuterated and tritiated versions (TA Kochina, DV Vrazhnov, EN Sinotova, VV Avrorin, MY Katsap, YV Mykhov, Russ J

Gen Chem + 2002, 72, 1222; EA Shishigin, VV Avrorin, TA Kochina, Sinotova EN, Russ J Gen Chem + 2005, 75, 152); the C0 ₂ marked ⁿ C or ^{! 4} C is the main source of ^U C and ¹⁴ C is obtained by acidification of barium carbonate labeled Ba ¹⁴ C0 ₃ (R. Voges, JR Heys, T. Moenius, Preparation of Compounds Labeled with Tritium and Carbon-14, Wiley- VCH: Chippenham (UK) 2009).

According to a preferred variant of the invention, in the process for preparing compounds marked oxyboranes of formula (I), the C0 ₂ C0 ₂ used is marked wherein C represents a C ^U isotope, ⁱ³ C or ¹⁴ C.

According to another preferred variant of the invention, in the process for the preparation of labeled oxyborane compounds of formula (I), the hydroborane used is a hydroborane

1 2 2

labeled with formula R R BH wherein H represents deuterium (H) or tritium (¾).

According to yet another preferred variant of the invention, in the process for the preparation of labeled oxyborane compounds of formula (I), the C0 ₂ and the hydroborane used are both labeled: C (½ is C0 ₂ labeled in where C represents an isotope ⁿ C, ^I3 C or ¹⁴ C, the hydroborane is a labeled hydroborane of formula R ^ BH

2 3

wherein H represents deuterium (H) or tritium (H).

The ¹⁴ C labeled molecules have contributed to many advances in life sciences (enzymatic mechanisms, biosynthetic mechanisms, biochemistry), environmental sciences (tracing of waste), research (elucidation of reaction mechanisms) or the diagnosis. , research and development of new pharmaceutical and therapeutic products. The ¹⁴ C-labeled molecules have, in fact, an advantage for metabolic studies because ¹⁴ C is easily detectable and quantifiable in vitro medium as in vivo.

The main source of C ⁱ⁴ ¹⁴ is C0 ₂ which is obtained by acidification of barium carbonate Ba ¹⁴ C0 _3. The development of basic molecule synthesis processes for the development of drugs is therefore essential to produce ¹⁴ C labeled active ingredients whose metabolism can thus be determined (R. Voges, JR Heys, T. Moenius, Preparation of Compounds Labeled with Tritium and Carbon-14, Wiiey-VCH: Chippenham (UK) 2009.

The major constraint limiting the synthesis of labeled molecules C ⁱ is the need for a high yield of product ¹ C formed relative to the amount of C0 ₂ used ¹⁴ and rest on a small number of steps in order to minimize costs associated with the use of Ba ¹⁴ C0 ₃ (Pleiss U, R. Voges, Synthesis and Applications of Isotopically Labeled Compounds, Volume 7, WIley-VCH, 2001; R. Voges, JR Heys, T. oenius, Preparation of Compounds Labeled with Tritium and Carbon-14, Wiley-VCH: Chippenham (U) 2009).

The method according to the invention meets these requirements because the working pressure C0 ₂ can be low, for example from 0.2 to 1 bar. In addition, the C0 ₂ incorporation rate (or yield relative to the C0 ₂ introduced) remains high, and may, for example, exceed 95%.

The conditions of temperature, reaction time and solvent, as well as the quantities of reagents and catalysts used in the process for the preparation of the labeled oxyborane compounds of formula (F), are those previously described as part of the preparation process. oxyborane compounds of formula (I).

The subject of the invention is the use of the labeled oxyborane compounds of formula (I) obtained according to the process of the invention, for the preparation of the marked derivatives of methane, in particular, oxygenated, halogenated or aminated derivatives of methane, in particular formic acid, formaldehyde, methanol, methane, methyl halide, methylamine.

The resulting methane-labeled derivatives can then be used in the manufacture of vitamins, pharmaceuticals, glues, acrylic fibers and synthetic leathers, pesticides, and fertilizers, for example. This is another object of the invention.

The invention also relates to a process for producing vitamins, pharmaceuticals, glues, acrylic fibers, synthetic leathers, pesticides, and fertilizers, for example, comprising a step of preparing the marked derivatives of methane, in particular in particular, oxygenated, halogenated or amine derivatives of methane from labeled oxyborane compounds of formula (I) obtained by the process according to the invention.

The invention further relates to a method of manufacturing tracers and radiotracers, characterized in that it comprises a step of preparation of the labeled derivatives of methane, in particular, oxygenated, halogenated or amine derivatives of methane, from labeled oxyborane compounds of formula (I) obtained by the process according to the invention.

Other advantages and features of the present invention will appear on reading the examples below given for illustrative and non-limiting. EXAMPLES

EXAMPLE 1

The catalytic reaction of C0 ₂ hydroboration in methanol, shown in Scheme 5 below, was carried out according to the following experimental protocol.

Under an inert atmosphere, in a glove box, the hydroborane R ⁵ R ² BH (1 equivalent), the pre-catalyst (0.0001 to 1 molar equivalent) and the solvent are introduced into a Schlenk tube which is then sealed with a J. Young tap. The hydroborane concentration in the reaction mixture is about 0.5 mol.L- ¹ (concentration calculated on the basis of the volume of solvent introduced) .The order of introduction of the reagents does not matter.

Schlenk is then pressurized with C0 ₂ (from 1 to 3 bar) using a vacuum ramp and then heated to a temperature between 25 and 100 ° C until the total conversion of C0 ₂ ( from 5 minutes to 72 hours of reaction).

Once the reaction is complete, the resulting oxyborane compound is hydrolysed. For this purpose, a volume of water equal to the volume of solvent is added with a syringe and the mixture is stirred at room temperature for 1 hour. The volatile products are transferred, under reduced pressure, into a second Schlenk tube leading to the production of an aqueous solution of methanol.

The results are shown in Table 1 below, giving examples of conversions of CO ₂ to methoxyborane and, after hydrolysis, its conversion to methanol. At 20 ° C, the maximum observed TOF is 288 h ^-1 (for BV ^Me as catalyst) and the maximum measured TON is 2014 (with BV ^Me as catalyst).

CH ₃ OH

Figure 5

Different hydroboranes, catalysts, solvents and temperatures were tested for the reaction. The catalysts Me-TBD-BBN *, (TDB-BBN) ₂ , TBD-BBN-CO ₂ and TBD-BBN-BBN used in this example were prepared according to the following protocols:

- Synthesis of (TBD-BBN)?

A 20 mL flask equipped with a magnetic bar and closed with a J. Young cap is loaded with TBD (163.1 mg, 1.17 mmol, 1 eq), dimer (9-BBN) ₂ (143 0 mg, 0.59 mmol, 0.5 eq) and tetrahydrofuran (3.5 mL). The flask is closed and the solution is stirred for one hour at 70 ° C. The reaction mixture is cooled to room temperature then the solid is filtered on iritated and washed with diethyl ether. A white solid is recovered and dried under reduced pressure to obtain the product (TBD-BBN) ₂ with a yield of 75% (194.9 mg).

. Synthesis of TBD-BBN-CQ

A 20 mL flask equipped with a magnetic bar and closed with a J. Young plug was loaded with (TBD-BBN) ₂ (71.0 mg, 0.14 mole) and tetrahydrofuran (4 mL). The reaction mixture is placed under a CO ₂ atmosphere (1 bar). The flask is closed and the solution is stirred for 75 minutes at 100 ° C. The white solid in the reaction mixture gradually solubilizes during heating. The reaction mixture was cooled to room temperature (about 20 ° C) and then the solvent was evaporated under reduced pressure to recover TBD-BBN-CO ₂ as a white solid in quantitative yield (84.0 mg). - Synthesis of TBD-BBN-BBN

A 20 mL flask equipped with a magnetic bar and closed with a J. Young plug is loaded with (TBD-BBN) ₂ (100.0 mg, 0.19 mmol, 1 eq), dimer (9- BBN) ₂ (51.0 mg, 0.21 mmol, 1.1 eq) and tetrahydrofuran (5 mL). The flask is closed and the solution is stirred for 150 minutes at 00 ° C. The white solid in the reaction mixture gradually solubilizes during heating. The reaction mixture is cooled to room temperature and then the solvent is partially evaporated from the reaction mixture to about 0.5 mL. During evaporation of the solvent, a white solid appears. The solid is filtered on fried and washed with cold diethyl ether (-40 ° C). The solid is recovered and dried under reduced pressure to obtain the TBD-BBN-BBN product with a yield of 76% (110.5 mg).

^" Synthesis of MeTBD-BBN ^+" A 20 mL flask equipped with a magnetic bar and closed with a J. Young plug is loaded with MTBD (53.1 mg, 0.35 mmol, 1 eq) and tetrahydrofuran (3.5 mL). The solution is stirred and a solution of 1M 9-iodo-9-borabicyclo [3.3.1] nonane in hexane (350 μί, 0.35 mmol, 1 eq) is added to the reaction mixture. A white precipitate forms immediately after addition of the 9-iodo-9-borabicyclo [3.3.1] nonane solution. The flask is closed and the solution is stirred for 30 minutes at room temperature (about 20 ° C). The solid is sintered and washed with diethyl ether. The solid is recovered and dried under reduced pressure to obtain MeTBD-BBN ⁺ I ^'product with a yield of 81% (112.0 mg).

Table 1

R'R ² B Catalyst Amount of Solvent Temp. Time Yield Yield

H catalyst -rature of methoxy-

(eq mol) * (° C) Borane methanol reaction

(h) (%) (%)

9-BBN TBD 0.025 THF 20 27 90 85

9-BBN TBD 0.01 THF 20 23 89 85

9-BBN TBD 0.001 THF 20 147 95 90

9-BBN Me-TBD 0.025 THF 20 7 93 87

9-BBN Me-TBD 0.0 THF 20 24 81 76

9-BBN DBU 0.025 THF 20 7 91 85

9-BBN DBU 0.01 20 17 100 96

9-BBN (TBD-BBN) ₂ 0.012 THF 20 166 80 75

9-BBN TBD-BBN-0.025 THF 20 7 66 63 co ₂

9-BBN TBD-BBN-0.025 THF 70 47 97 92

BBN

9-BBN NEt ₃ 0.025 THF 20 28 98 94

9-BBN arginine 0.025 THF 20 14 92 86

9-BBN DMAP 0.025 THF 70 42 95 89

9-BBN dppe 0.025 THF 20 24 100 95

9-BBN PCy ₃ 0.025 THF 20 5 94 89

9-BBN Pl-t-Bu 0.025 THF 20 18 100 92

9-BBN BV ^Me 0.025 THF 20 1 87 83

9-BBN BV ^e 0.01 THF 20 3 95 90

9-BBN BV ^Me 0.005 THF 20 3 95 89

9-BBN BV ^Me 0.005 THF 70 0.4 94 89

9-BBN BV ^Me 0.001 THF 20 19 95 90

9-BBN BV ^Me 0.0001 THF 20 192 95 90

9-BBN BV ^Me 0.0001 THF 70 144 96 91

9-BBN BV ^iBu 0.025 THF 20 1 98 94 9-BBN ItBu 0.025 THF 20 1.5 90 86

9-BBN ItBu 0.025 THF 70 0.2 100 96

9-BBN ItBu 0.005 THF 70 0.7 98 94 catBH Me-TBD 0.01 THF 20 163 98 93 catBH TBD-BBN-0.025 THF 20 155 90 85

C0 ₂

9-BBN TBD 0.025 benzene 20 170 97 92

9-BBN TBD 0.025 toluene 20 170 97 92

9-BBN PyO 0.025 THF 20 20 96 90

9-BBN Me-TBD-0.025 THF 20 4 89 85

ΒΒΝ ⁺ Γ

* The molar equivalent refers to the amount of hydroborane of formula (II),

These results show that, under the operating conditions indicated in Table 1, even in the presence of bulky catalysts and boranes, C0 ₂ can be converted into methoxyborane compounds with very good yields (at least 66%) and very good selectivity. . In turn, methoxyborane provides, after hydrolysis, methanol with very good yields (at least 63%).

EXAMPLE 2

The catalytic hydroformation reaction of C0 ₂ in formoxyborane, shown in Scheme 6 below, was carried out according to the experimental protocol indicated in Example 1. The results are shown in Table 2 below.

²²

Figure 6

Different catalysts have also been tested. In all cases, the solvent used is THF and the temperature of the reaction is 20 ° C.

Table 2

R'R¾H Catalyst Quantity of Yield Time in

Formoxyborane reaction catalyst

(eq mol) * (h) (%)

9-BBN TBD 0.025 0.1 35

9-BBN Me-TBD 0.025 0.1 45 9-BBN DBU 0.025 0.1 32

9-BBN NEt, 0.025 10 30

* The molar equivalent refers to the amount of hydroborane of formula (II).

These results show that, under the operating conditions indicated in Table 2, the CO ₂ can be converted into formoxyborane compounds with a mean to good yield (30 to 45%). Of the catalysts tested, Me-TBD was the most effective. The formoxyborane obtained can provide, after hydrolysis, formic acid.

EXAMPLE 3

The catalytic reaction for hydroboration of CO ₂ in bis (boryl) acetal, shown in Scheme 7 below, was carried out according to the experimental protocol indicated in Example 1. A set of results is presented below in Table 3 showing examples of CO ₂ conversions to bis (boryl) acetal.

Figure 7

Table 3

R'R ² BH Catalyst Quantity of Production Time in

catalyst reaction bis (boryl) acetal

(eq mol) * (h) (%)

9-BBN TBD 0.025 0.3 88

9-BBN Me-TBD 0.025 0.3 89

9-BBN DBU 0.025 0.3 79

9-BBN NEt ₃ 0.025 4.5 68

* The molar equivalent refers to the amount of hydroborane of formula (II). These results show that, under the operating conditions indicated in Table 3, the CO ₂ can be converted into bis (boryl) acetal with good to excellent yields (from 68 to 89%). Among the catalysts tested, the best results have been obtained. have been observed with triethylamine and TBD (triazabicyclodecene). The bis (boryl) acetal can provide, after hydrolysis, formaldehyde.

The abbreviations used are:

Me-TBD-BBN ⁺ I ^"

All these results show that the preparation of oxyborane compounds from CO ₂ and a hydroborane, in the presence of a large variety of catalysts is done under conditions of CO ₂ pressures and mild reaction temperatures and with good or very good performance and good or excellent selectivity (In some cases, 100% of the oxyborane compound is obtained). The oxyborane compounds thus obtained are sufficiently flexible to be converted into methane derivatives, in particular, oxygenated derivatives of methane, especially formic acid, formaldehyde and methanol.

EXAMPLE 4

The catalytic reaction for hydroboration of CO ₂ in methanol, presented in scheme 5 above, was carried out according to the experimental protocol presented in Example 1.

A set of results is shown in Table 4 below, giving examples of conversions of C0 ₂ to methoxyborane and, after hydrolysis, its conversion to methanol.

For a given catalyst, depending on the associated hydroborane, the minimum rotation frequency (TOF) observed is 0 h ^-1 (for IMes as catalyst with catBH or pinBH as hydroborane for example), up to a TOF observed maximum of 1.1 hr ^-1 (for Me-TBD as a catalyst with 9-BBN as hydroborane) and the maximum number of rotations (TON) measured is 8 (for Me-TBD as a catalyst with 9-BBN as hydroborane).

Table 4

Catalyst Quantity of Solvent Temp. Time Yield Yield

H catalyst -rature of methoxy-

(eq mol) * (° C) Borane methanol reaction

(he) (%) (%)

9-BBN TBD 0.025 THF 20 27 90 85 catBH TBD 0.025 THF 20 72 0 0 pinBH TBD 0.025 THF 20 72 0 0

9-BBN Me-TBD 0.025 THF 20 7 93 87 catBH Me-TBD 0.01 THF 20 163 98 93 pinBH Me-TBD 0.025 THF 20 72 0 0

9-BBN DBU 0.025 THF 20 7 91 85 catBH DBU 0.025 THF 20 0 0 0 pinBH DBU 0.025 THF 20 0 0 0

9-BBN IMes 0.025 THF 20 32 91 84 catBH IMes 0.025 THF 20 32 0 0 catBH IMes 0.002 THF 20 32 0 0

These results show that the preparation of oxyborane compounds from CO ₂ and a hydroborane, in the presence of a large variety of catalysts, requires a judicious choice between the catalyst and the associated hydroborane taking into account in particular their respective steric hindrance, the reducing character of the hydroborane, the nucleophilic nature of the catalyst, their solubility in the reaction medium.

Claims

1. Process for the preparation of oxyborane compounds of formula (I)

in which

^■ R ¹ and R ² represent, independently of one another, a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, heterocycle, a silyl group, a siloxy group, an amino group, an alkoxy group, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, silyl, siloxy, amino and alkoxy groups being optionally substituted, or

^■ R ¹ and R ² taken together with the boron atom to which they are attached form an optionally substituted heterocycle,

^■ Y represents -CHO, -CH ₂ ^-0-BR] R ² with R ¹ and R ² as defined above, -CH _3,

^■ R ^3, R ² and Y optionally comprise, independently of one another, H, C, N, O, F, Si and / or S as defined below,

- H represents a hydrogen atom (1H), deuterium ⁽² H) or tritium ⁽³ H), C represents a carbon atom ⁽¹² C), ^U C isotope, ¹³ C or ¹⁴ C.

N represents a nitrogen atom ( ^I N), a ¹⁵ N isotope,

O represents an oxygen atom ( ¹⁶ 0), an isotope ¹⁸ 0,

F represents a fluorine atom ( ^I9 F), an ¹⁸ F isotope,

Si represents a silicon atom (Si), an Si or Si isotope,

S represents a sulfur atom (S ^32), an isotope ³ S, ³⁴ S, or ³⁶ S, characterized in that reacting a hydroborane of formula (II) wherein R ^1, R ² and M are as defined above with C0 ₂ in which C and O are as defined above, and

in the presence of a catalyst selected from the group consisting of

1. organic bases selected from nitrogenous organic bases, phosphorus organic bases, carbon bases, or oxygenated organic bases;

ii. organic or inorganic boron compounds; or

iii. organic or inorganic compounds of aluminum.

2. Method according to claim 1, characterized in that

i ~ y

^■ R and R independently of one another, a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, said alkyl, aryl and alkoxy being optionally substituted, or

3. Method according to one of claims 1 or 2, characterized in that

^■ R ^s and R ² represent, independently of one another, a hydrogen atom; an alkyl group selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or their branched isomers, cyclohexyl; an aryl group selected from benzyl or phenyl; or

R ¹ and R ² taken together with the boron atom to which they are bonded form a heterocycle, said heterocycle being selected from catBH, pinBH or 9-BBN.

4. Method according to any one of claims I to 3, characterized in that the catalyst is (i) an organic base selected from nitrogenous organic bases, phosphorus organic bases, carbon bases, or oxygenated organic bases, with the nitrogenous organic bases being secondary or tertiary amines chosen from, for example, triazabicyclodecene (TBD), N-methyltriazabicyclodecene (MeTBD), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), trimethylamine, triethylamine, piperidine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo [2.2.2] octane (DABCO), proline, phenylalanine, a thiazolium salt, N-diisopropylethylamine (DIPEA) or DIEA), arginine; phosphazenes chosen from, for example, tert-butyliminothrid (dimethylamino) phosphorane (P-t-Bu), tert-butylimino-tri (pyrrolidino) phosphorane (BTPP), tetramethyl (tris (dimethylamino) phosphoranylidene) phosphorictriamide; And imine (P2-Et), tert-octylimmo-tris (dimethylamino) phosphorane (P-t-Oct) and 1-tert-butyl-4,4,4-tris (dimethylamino) -2,2-bis [tris ( dimethylamino) - hos hora ylidenami o] -2λ5,4λ5-catenadi (hos hazene) (P4-Bu);

the phosphorus-containing organic bases being alkyl or aryl phosphines chosen from triphenylphosphine, 2,2'-bis (diphenylphosphino) -1,2-binaphthyl;

(ΒΓ ΑΡ), triisopropylphosphine, 1,2-bis (diphenylphosphino) ethane (dppe), tricyclohexylphosphine (PCy ₃ ); alkyl and aryl phosphonates selected from diphenylphosphate, triphenylphosphate (TPP), tri (isopropylphenyl) phosphate (TIPP), cresyldiphenyl phosphate (CDP), tricresylphosphate (TCP); alkyl and aryl phosphates selected from di-n-butyl phosphate (DBP), tris- (2-ethylhexyl) phosphate, triethyl phosphate; alkyl and aryl phosphinites and phosphonites selected from methyldiphenylphosphinite and methyldiphenylphosphonite; the aza-phosphines chosen from 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane (BV ^Me ) and 2,8,9-triisobutyl-2, 5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane (BV ^lBu );

the carbon bases being N-heterocyclic carbenes derived from an imidazolium salt selected from 1,3-bis (2,6-diisopropylphenyl) -1H-imidazol-3-ium, 1,3-bis (2 6-diisopropylphenyl) -4,5-dihydro-1H-imidazol-3-ium, 1,3-bis (2,4,6-trimethylphenyl) -1H-imidazol-3-ium, 1,3-bis (2) 4,6-trimethylphenyl) -4,5-dihydro-1H-imidazol-3-diol, 4,5-dichloro-1,3-bis (2,6-diisopropylphenyl) -1H-imidazol-3- ium, 1,3-di-tert-butyl-1H-imidazol-3-lithium or carbene ItBu, 1,3-di-tert-butyl-4,5-dihydro-1H-imidazol-3-ium, said salts being in the form of chloride salts; or

the oxygenated bases chosen from hydrogen peroxide, benzoyl peroxide, pyridine oxide (PyO), N-methylmorpholine oxide or 1-λ ¹ -oxanyl-2,2,6,6- tetramethylpiperidine.

5. A method according to any one of claims 1 to 3, characterized in that the catalyst is (ii) an organic or inorganic compound of boron selected from BF _3, BF ₃ (Et ₂ 0), the BC1 _3, triphenyl hydroborane, tricyclohexyl hydroborane, B (C ₆ F ₅ ) ₃ , B-methoxy-9-borabicyclo [3.3.1] nonane, B-benzyl-9-borabicyclo [3.3.1] nonane (B- methoxy-9BBN), Me-TBD-BBN ⁺ Γ, Me-TBD-BBN ⁴ CF ₃ S0 ₃ ^" , (TDB-BBN) ₂ , TBD-BBN-C0 ₂ or TBD-BBN-BBN.

6. A method according to any one of claims 1 to 3, characterized in that the catalyst is (iii) an organic or inorganic aluminum compound selected from A1C1 ₃₅ AlBr _3, î'isopropoxyde aluminum or Péthanoate of aluminum.

7. Process according to any one of Claims 1 to 4, characterized in that the catalyst is (i) an organic base chosen from

nitrogenous bases, in particular triazabicyclodecene (TBD), N-methyltriazabicyclodecene (MeTBD), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), arginine; phosphazenes chosen from, for example, tert-butyliminothrid (dimethylamino) phosphorane (P-t-Bu), tert-butylimino-tri (pyrrolidino) phosphorane (BTPP), tetramethyl (tris (dimethylamino) phosphoranylidene) phosphorictriamid -Et-imine (P2-Et), tert-octylimino-tris (dimethylamino) phosphorane (Pl-t-Oct) and 1-tert-butyl-4,4,4-tris (dimethylamino) -2,2- bis [tris (dimethylamino) -phosphoranylidenamino] -2λ5,4λ-catenadi (hos hazene) (P4-Bu);

phosphorus bases, especially 1,2-bis (diphenylphosphino) ethane (dppe), tricyclohexylphosphine (PCy ₃ ), 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo [ 3.3.3] undecane (BV ^Me ), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane (BV ^lBu );

pyridine oxide (PyO); or

1,3-di-tert-butyl-1H-imidazol-3-ium or carbene ItBu.

8. Process according to any one of claims 1 to 7, characterized in that the reaction is carried out under a CO ₂ pressure of between 0.2 and 75 bar, preferably between 0.2 and 30 bar, more preferably between 1 and 10 bars, terminals included.

9. Method according to any one of claims 1 to 8, characterized in that the reaction is carried out at a temperature between 20 and 150 ° C, preferably between 20 and 125 ° C, more preferably between 20 and 70 ° C , terminals included.

10. Method according to any one of claims 1 to 9, characterized in that the reaction is carried out for a period of 5 minutes to 300 hours, preferably 2 minutes to 250 hours, preferably 10 minutes to 200 hours, terminals included.

11. Process according to any one of Claims 1 to 10, characterized in that the reaction is carried out in one or a mixture of at least two solvent (s) chosen from:

ethers, preferably diethyl ether, or THF;

hydrocarbons, preferably benzene or toluene;

the nitrogenous solvents, preferably pyridine, or acetonitrile;

sulfoxides, preferably dimethyl sulphoxide;

alkyl halides, preferably chloroform, or methylene chloride.

12. Process according to any one of Claims 1 to 1 1, characterized in that the concentration of the hydroborane of formula (II) is from 0.1 to 2 mol / l, preferably from 0.3 to 1.5 mol / l. more preferably from 0.5 to 1.5 mol / L.

13. Method according to any one of claims 1 to 12, characterized in that the amount of catalyst is from 0.00001 to 1 molar equivalent, preferably from 0.0001 to 0.1 molar equivalents, more preferably from 0.001 to 0.1 molar equivalent, limits included, relative to the hydroborane of formula (II).

14. Use of the oxyborane compounds of formula (I) obtained by the process according to any one of claims 1 to 13, for the preparation of optionally labeled methane derivatives, in particular, oxygenated, halogenated or amine derivatives of methane, in particular formic acid, formaldehyde, methanol, methane, methyl halide, methylamine.

15. A method of manufacturing vitamins, pharmaceuticals, glues, acrylic fibers, synthetic leathers, pesticides, and fertilizers, comprising a step of preparing optionally labeled methane derivatives, in particular, oxygenated derivatives, halogenated or methane amines, from oxyborane compounds of formula (I) obtained by the process according to any one of claims 1 to 13.

16. A method of manufacturing tracers and radiotracers, characterized in that it comprises a step of preparation of the marked derivatives of methane, in particular, oxygenated, halogenated or amine derivatives of methane, from oxyborane compounds. labeled compounds of formula (I) obtained by the process according to any one of claims 1 to 13.